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Variable Control of Ets-1 DNA Binding by Multiple Phosphates in an Unstructured Region

Authors :
Algirdas Velyvis
Hyun Seo Kang
Gregory M. Lee
Lewis E. Kay
Mary L. Nelson
Miles A. Pufall
Lawrence P. McIntosh
Barbara J. Graves
Source :
Science. 309:142-145
Publication Year :
2005
Publisher :
American Association for the Advancement of Science (AAAS), 2005.

Abstract

Cell signaling that culminates in posttranslational modifications directs protein activity. Here we report how multiple Ca 2+ -dependent phosphorylation sites within the transcription activator Ets-1 act additively to produce graded DNA binding affinity. Nuclear magnetic resonance spectroscopic analyses show that phosphorylation shifts Ets-1 from a dynamic conformation poised to bind DNA to a well-folded inhibited state. These phosphates lie in an unstructured flexible region that functions as the allosteric effector of autoinhibition. Variable phosphorylation thus serves as a “rheostat” for cell signaling to fine-tune transcription at the level of DNA binding.

Details

ISSN :
10959203 and 00368075
Volume :
309
Database :
OpenAIRE
Journal :
Science
Accession number :
edsair.doi.dedup.....244196419b1446b7867b5d096b7de02a
Full Text :
https://doi.org/10.1126/science.1111915